Drugs That Target Th17 Cells Can Improve Debilitating Skin Disease Hidradenitis suppurativa

MedicalResearch.com Interview with:

Dr Jean Fletcher Assistant Professor Schools of Medicine and Biochemistry & Immunology Trinity College Dublin, the University of Dublin Dublin, Ireland

Hidradenitis suppurativa
Wikipedia image

Dr Jean Fletcher
Assistant Professor
Schools of Medicine and Biochemistry & Immunology
Trinity College Dublin, the University of Dublin
Dublin, Ireland

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Hidradenitis suppurativa (HS) is an inflammatory skin disease which causes deep, painful lesions in areas such as the underarms and groin. 1-4% of people are thought to suffer from the disease, however as it is under recognised and often misdiagnosed these may be conservative estimates. The pain and distress associated with HS leads to a poor quality of life with many patients experiencing depression.
Current interventions include combinations of antibiotics, surgery to remove lesions and more recently the use of the biologic therapies such as TNF inhibitors; however these are often ineffective and there is a pressing need for more effective treatments.

The cause of Hidradenitis suppurativa is unknown, however there are known risk factors which include smoking and obesity, and there is an association with inflammatory bowel disease, which suggests that dysregulation of the immune system may play a role.

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Study Reports Hair Repigmentation During Immunotherapy For Lung Cancer

MedicalResearch.com Interview with:
Dr. Noelia Rivera MD

Dermatologist
Hospital Universitari Germans Trias i Pujol, Badalona
Universitat Autònoma de Barcelona

MedicalResearch.com: What is the background for this study?

Response: In the last few years some new therapies targeting immune checkpoints have been developed. The programmed death receptor-1 (PD-1) are immune checkpoints that prevent the immune system to act against own tissues. By blocking these mediators it is possible to prevent tumors to escape from the immune system.

About half of the patients receiving these therapies will develop mild to moderate cutaneous adverse events. In the pre-authorization studies for malignant melanoma these include rash, vitiligo, and pruritus. “Rash” has commonly been reported as an adverse event in many oncologic trials evaluating the drugs, without providing further information about the clinical or histological details. Lately, lichenoid eruptions associated to these therapies have been reported and it suggests that an important percentage of these reactions present lichenoid histological features.

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Lithium May Reduce Melanoma Risk and Mortality

MedicalResearch.com Interview with:

Maryam M. Asgari, MD, MPH Department of Dermatology Massachusetts General Hospital, Department of Population Medicine Harvard Medical School, Boston, Massachusetts Division of Research, Kaiser Permanente Northern California, Oakland 

Dr. Asgari

Maryam M. Asgari, MD, MPH
Department of Dermatology
Massachusetts General Hospital,
Department of Population Medicine
Harvard Medical School, Boston, Massachusetts
Division of Research, Kaiser Permanente
Northern California, Oakland 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response:  Laboratory studies show lithium, an activator of  the Wnt/ß-catenin signaling pathway, slows melanoma progression, but no published epidemiologic studies have explored this association. We conducted a retrospective cohort study of adult white Kaiser Permanente Northern California members (n=2,213,848) from 1997-2012 to examine the association between lithium use and melanoma risk.

Our main finding is that lithium-exposed individuals had a reduced incidence of melanoma, did not develop very thick tumors (> 4 mm Breslow depth) or extensive disease at presentation, and had decreased melanoma-specific mortality compared to unexposed individuals suggesting a possible role for lithium in altering melanoma risk.

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Higher HIV Viral Loads Linked to Increased Squamous Cell Cancers of Skin

MedicalResearch.com Interview with:

Maryam M. Asgari, MD, MPH Department of Dermatology, Massachusetts General Hospital, Department of Population Medicine Harvard Medical School, Boston, Massachusetts Division of Research, Kaiser Permanente Northern California, Oakland

Dr. Asgari

Maryam M. Asgari, MD, MPH
Department of Dermatology
Massachusetts General Hospital,
Department of Population Medicine
Harvard Medical School, Boston, Massachusetts
Division of Research, Kaiser Permanente
Northern California, Oakland

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Nonmelanoma skin cancer – defined as basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) – is a common malignant condition, affecting more than 2 million Americans every year. BCCs are more common than SCCs among individuals with healthy immune systems, while SCCs are more predominate than BCCs among people who are immunocompromised.

We examined how laboratory markers used to evaluate HIV disease progression may be associated with subsequent nonmelanoma skin cancer risk in white patients previously diagnosed with at least one such cancer from 1996 to 2008.  We measured CD4 count, viral load and subsequent nonmelanoma skin cancer. The study included 455 participants with HIV and 1,952 without HIV. All were members of the Kaiser Permanente Northern California health care plan.

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Clinical Perineural Invasion of Cutaneous SCC May Warrant Adjuvant Treatment

MedicalResearch.com Interview with:
Dr. Chrysalyne D. Schmults, MD, MSCE
Associate Professor of Dermatology, Harvard Medical School
Director, Mohs and Dermatologic Surgery Center and
Mr. Pritesh S. Karia, MPH
Department of Epidemiology
Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland

Department of Dermatology
Brigham and Women’s Faulkner Hospital
Harvard Medical School, Boston, Massachusetts
Jamaica Plain, MA 02130-3446 

MedicalResearch.com: What is the background for this study?

Response: Perineural nerve invasion (PNI) is a well-recognized risk factor for poor prognosis in patients with cutaneous squamous cell carcinoma (CSCC). Most cases of CSCC with PNI are identified on histologic examination at the time of surgery and the patient has no clinical symptoms or radiologic evidence of PNI. These cases are classified as incidental PNI (IPNI). However, some patients with PNI present with clinical symptoms and/or radiologic evidence of PNI. These cases are classified as clinical PNI (CPNI). A few studies have shown differences in disease-related outcomes between CSCC patients with IPNI and CPNI but consensus regarding adjuvant treatment and detailed guidelines on follow-up schedules have not yet materialized.

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Google Searches Valuable Source of Cancer Incidence and Mortality Data

MedicalResearch.com Interview with:

Mackenzie R. Wehner, MD, MPhil Department of Dermatology University of Pennsylvania Philadelphia, PA

Dr. Weher

Mackenzie R. Wehner, MD, MPhil
Department of Dermatology
University of Pennsylvania
Philadelphia, PA

MedicalResearch.com: What is the background for this study?

Response: For some diseases, we have national registries, in which information about every person with that disease is entered for research purposes. For other diseases, unfortunately, we do not have such registries. There are growing opportunities to use information like internet searches to better understand behaviors and diseases, however. Our study was a proof-of-concept: we aimed to find out whether internet searches for diseases correlated with known incidence (how many people are diagnosed with the disease) and mortality (how many people die of the disease) rates. E.g. does the number of people who searched ‘lung cancer’ online correlate with the number of people who we know were diagnosed with or who died of lung cancer during that same time period? This is important to know if researchers in the future want to use internet search data for diseases where we lack registry information.

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When Interpreting Skin Biopsies, Pathologists Often Disagree

MedicalResearch.com Interview with:

Joann G. Elmore M.D., M.P.H. Professor of Medicine,  Adjunct Professor of Epidemiology, University of Washington School of Medicine Harborview Medical Center Seattle, WA 98104-2499

Dr. Elmore

Joann G. Elmore M.D., M.P.H.
Professor of Medicine,
Adjunct Professor of Epidemiology,
University of Washington School of Medicine
Harborview Medical Center
Seattle, WA 98104-2499

MedicalResearch.com: What is the background for this study?

JE: Previous studies on diagnostic accuracy in interpreting melanocytic lesions exist but have small sample size, inclusion of experts only, or small numbers of specimens. We sought to examine accuracy and reproducibility in melanocytic skin lesions by improving upon the methodological limitations of previous studies. Specifically, we recruited a large national sample of practicing community and academic pathologists with a wide range of experience, and we utilized a large sample of biopsy cases that were carefully selected. Given that diagnostic errors can lead to patient deaths and invasive melanoma kills more than 9,000 Americans each year, we wanted to study the issue of diagnostic accuracy in interpreting melanocytic skin lesions in a very robust fashion.

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Why Does Some Eczema Persist Into Adulthood?

MedicalResearch.com Interview with:

Dr. Katrina Abuabara MD, MA, MSCE University of California San Francisco

Dr. Abuabara

Dr. Katrina Abuabara MD, MA, MSCE
University of California San Francisco

MedicalResearch.com: What is the background for this study?

Response: Atopic dermatitis (synonymous with atopic eczema or just “eczema”) is a common and burdensome condition that often presents in childhood but can occur in individuals of any age. It is episodic, meaning that it waxes and wanes over time, and many patients will have periods without signs or symptoms of the disease. Conventional wisdom suggests that “most children” improve by adolescence, but prior studies have not had sufficiently frequent follow-up to detect episodic disease beyond childhood.

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FDA Approves BAXDELA™ (Delafloxacin) For Skin Infections

MedicalResearch.com Interview with:

Dr. Sue Cammarata, MD Chief Medical Officer Melinta Therapeutics

Dr. Cammarata

Dr. Sue Cammarata, MD
Chief Medical Officer
Melinta Therapeutics

MedicalResearch.com:   Would you explain what is meant by MRSA?

Response: MRSA is methicillin-resistant Staphylococcus aureus, a type of staph bacteria that is  resistant to many antibiotics. MRSA is noted by the CDC as one of the top 18 drug-resistant bacteria threats to the United States.  (from CDC https://www.cdc.gov/drugresistance/biggest_threats.html  ) 

MedicalResearch.com:   Why is infection with MRSA so serious?

Response:  MRSA can cause skin infections, lung infection and other issues.

If left untreated, MRSA infections can become severe and cause sepsis – a life-threatening reaction to severe infection in the body – and even death.  MRSA can also cause major issues, such as bloodstream infectionspneumonia and surgical site infections in a healthcare setting, such as a hospital or nursing home. “Resistance to first-line drugs to treat infections caused by Staphlylococcus aureus—a common cause of severe infections in health facilities and the community—is widespread. People with MRSA (methicillin-resistant Staphylococcus aureus) are estimated to be 64% more likely to die than people with a non-resistant form of the infection.”  (quote from WHO website http://www.who.int/mediacentre/factsheets/fs194/en/  )   Continue reading

How Does HPV Virus Lead To Skin Cancer?

MedicalResearch.com Interview with:
Prof. Dr. med. Sigrun Smola
Institute of Virology, Saarland University
Homburg/Saar, Germany

MedicalResearch.com: What is the background for this study?

Response: Non-melanoma skin cancer (NMSC), the most common cancer in humans, is caused by UV-irradiation. The potential co-factor role of cutaneous genus beta-human papillomaviruses (beta-HPV) in skin carcinogenesis, particularly in immunosuppressed patients, has become a major field of interest. However, the underlying mechanisms were unclear.

The skin has natural mechanisms providing protection against UV-induced damage. One important factor suppressing UV-induced skin carcinogenesis is the transcription factor C/EBPα belonging to the CCAAT/enhancer binding protein family. C/EBPα can induce cellular differentiation and is regarded as a tumor suppressor in various tissues. When C/EBPα expression is blocked in these tissues, tumorigenesis is enhanced.

Another important factor is the microRNA-203. It has been shown to control “stemness” in normal skin by suppressing a factor called p63. In many tumors miR-203 expression is shut off releasing this “brake”.

In our study we demonstrate that cutaneous beta-HPV interferes with both protective factors providing an explanation how cutaneous beta-HPV enhances the susceptibility to UV-induced carcinogenesis. Moreover, we provide evidence that these viruses regulate miR-203 via C/EBPα.

We have investigated this mechanism in Epidermodysplasia verruciformis (EV) patients that serve as a human model disease for studying the biology of genus beta-HPVs. They are highly susceptible to persistent genus beta-HPV infection, such as HPV8, and have an increased risk to develop non-melanoma skin cancer at sun-exposed sites.

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